Dr. Jim Sun will be starting as an Assistant Professor in July 2017. His research will focus on the complex interaction between the Mycobacterium tuberculosis and the macrophage and to develop new promising host-directed therapy to treat tuberculosis.
What is your background?
I am a cellular microbiologist who is specialized in host-pathogen interactions between the macrophage and Mycobacterium tuberculosis (Mtb). I grew up in Vancouver and earned my undergraduate degree in Biochemistry and my PhD in Experimental Medicine, both at the University of British Columbia. I was then recruited as postdoc to the deep south in Alabama (UAB) by Dr. Michael Niederweis, an internationally recognized leader in mycobacterial outer membrane physiology. There, I made the seminal discovery of a novel protein toxin produced by Mtb, and characterized its biochemical function and immunological effect on the host macrophage. In the latter part of my postdoc training at UAB, I developed my own research program under the mentorship of Dr. Olaf Kutsch, to discover host signaling pathways undermined during Mtb infection. I am looking forward to establishing my research program at uOttawa to continue my vision of uncovering all the key macrophage regulatory pathways involved in TB pathogenesis, which will pave the way for the development of alternative therapies against tuberculosis.
Tell us about your research?
The macrophage is a powerful innate immune cell capable of exterminating virtually all pathogenic microorganisms. However, Mtb reprograms host macrophages to deprive their killing ability, allowing the bacteria to remain hidden from the immune response and protected from drug therapy while inside these cells. With the emergence of multi-drug resistant TB coupled with the lack of novel anti-tuberculosis drugs, there is an urgent need for the development of alternative approaches to treat TB. Host-directed therapy (HDT), which targets host cells rather than the bacteria itself offers a promising alternative as this strategy will circumvent development of antibiotic resistance and the need for drugs to penetrate the impermeable Mtb cell wall. The overarching goal of my research is thus to discover and characterize host macrophage signaling pathways that are hijacked by Mtb during infection. This research will lead to the identification of novel and attractive targets that would be suitable for HDT.
What are some applications of your work?
The identification of host signaling pathways involved in the pathogenesis of Mtb has major implications on the advancement of host-directed TB therapy. As macrophages are naturally capable of destroying invading bacteria, the concept of HDT seeks to either (1) boost host immunity by enhancing the antibacterial mechanisms of macrophages to kill Mtb, or (2) deny Mtb from a required host pathway necessary for its intracellular survival. One particular application is a “release and kill” strategy, where Mtb-infected macrophages are forced into programmed cell death, or apoptosis, by specific drugs targeting a pathway required by Mtb to persist. Following apoptosis, the released Mtb could be killed by lower concentrations of standard anti-TB drugs, which is normally less effective against Mtb contained within macrophages. If developed to clinical application, this could mean greatly shortening the currently lengthy treatment periods (> 6 months) for TB patients. Furthermore, restoring the ability of macrophages to kill Mtb may also benefit treatment of other infectious diseases caused by intracellular pathogens.
What got you interested in tuberculosis?
Despite my undergraduate background in biochemistry, I would be lying if I told you I really enjoyed organic chemistry (who does right?). I was first introduced to the world of host-pathogen interactions during my PhD under the supervision of Dr. Zakaria Hmama, who more specifically termed this work as “cellular mycobacteriology”. During this time, I discovered virulence factors of Mycobacterium tuberculosis (Mtb) and characterized how they would impact the phagolysosome fusion program within macrophages. My passion for tuberculosis research was solidified as I became fascinated by how this bug could co-evolve with humans for thousands of years and to date remains a global health threat. I also realized that simply studying the bacteria is not enough and that to truly understand its pathogenesis, one must study the complex interactions between Mtb and the host macrophage. Research on host-directed therapy for TB is relatively new, but highly promising and exciting as it offers significant opportunities for discovery.
What’s the most interesting thing about you that we wouldn't learn from your resume?
I love travelling to explore new places where I can appreciate different cultures and history. I believe that despite the busy schedules of research in academia, one should always find time to travel. Recently, I had a chance to travel to Europe for the first time and was blown away by how unique it was compared to other places around the world. I enjoyed everything from the curbside coffee shops to huge museums in Paris, the splendid architecture and history of Rome, and the peace and tranquility of Venice. The part of traveling that I enjoy the most is the diversity of food that I get to experience. I have to admit that I am a rather big foodie coming from Vancouver, where you can get relatively authentic cuisines from all over the world. I look forward to trying some of the specialties that Ottawa has to offer (so far I have tried beaver tails and lobster poutine and they did not disappoint).